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Deubiquitinating enzyme PSMD14 promotes tumor metastasis through stabilizing SNAIL in human esophageal squamous cell carcinoma.

Cancer Lett.2018 Apr 01;418:125-134. Epub 2018 Jan 10
Rui Zhu 1 , Yongshuo Liu 2 , Honghong Zhou 1 , Lei Li 1 , Yi Li 1 , Fang Ding 1 , Xiufeng Cao 3 , Zhihua Liu 4
Rui Zhu 1 , Yongshuo Liu 2 , Honghong Zhou 1 , Lei Li 1 , Yi Li 1 , Fang Ding 1 , Xiufeng Cao 3 , Zhihua Liu 4
+ et al

[No authors listed]

Author information
  • 1 State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, PR China.
  • 2 State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, PR China; Department of Clinical Laboratory, Binzhou Medical University Hospital, Binzhou, Shandong 256603, PR China.
  • 3 Department of Surgical Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, PR China.
  • 4 State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, PR China. Electronic address: liuzh@cicams.ac.cn.

摘要


The epithelial-mesenchymal transition (EMT) transcription factor SNAIL is associated with distant metastasis and poor prognosis of esophageal squamous cell carcinoma (ESCC) patients. The proteolysis of SNAIL is mediated by the ubiquitin-proteasome system. Several E3 ligases have been characterized to promote SNAIL ubiquitination and degradation. However, the reverse process - deubiquitination of SNAIL remains largely unknown. In this study, we performed a mass spectrometry to examine the interaction between SNAIL and deubiquitinating enzyme(s). Subsequently, the deubiquitinating enzyme PSMD14 was identified to target SNAIL for deubiquitination and stabilization. Furthermore, knockdown of PSMD14 significantly blocks SNAIL-induced EMT and then suppresses tumor cell migration and invasion in vitro and tumor metastasis in vivo. In addition, the high expression level of PSMD14 predicts poor prognosis for esophageal cancer patients. These findings suggest PSMD14 as a bona fide deubiquitinating enzyme to regulate SNAIL at the post-translational level and provide a promising therapeutic strategy against tumor metastasis of esophageal cancer.

KEYWORDS: Deubiquitination, Esophageal squamous cell carcinoma, PSMD14, SNAIL, Tumor metastasis